Recent studies on the development of Plasmodium falciparum in the mature human erythrocyte a quiescent cell lacking all organelles and machinery to synthesize proteins, has suggested the presence of an extensive protein secretory pathway. Plasmodium proteins are transported through ER/Golgi-like infrastructure within the parasite and certain proteins are further exported from the parasitophorous vacuole membrane to the cytoplasm of erythrocyte through a tubovesicular network. To help define the protein secretory pathway in the malaria parasite at the molecular level, we have decided to investigate the role of two small GTP-binding proteins, Rab and Arf which control vesicular transport in all eukaryotic cell types examined thus far. We have identified several cDNA clones encoding Rab and Arf homologues from a Plasmodium falciparum lgt11 library. A PfRab1 protein, demonstrating extensive homology to the mammalian Rab 1 and yeast YPT1, displays typical features of the Ras-like GTP-binding domains and a geranylgeranlyation motif on its C-terminus. A PfArf1 protein contains an amino-terminal glycine for the myristoylation site and concensus sequences for GTP-binding motif. Rab1 and Arf1 proteins in eukaryotes are ubiquitously expressed and directly involved in vesicular transport from the ER to cis Golgi compartment. In Northern blot analysis, the PfRab1 transcript was detected exclusively in the sexual stages of gameotcytes and gametes/zygotes while the PfArf1 transcript was predominantly detected in the asexual erythrocytic stage in merozoites. The differential expression of PfArf and PfRab1 suggests that specific protein transport machinery may be evolved to accommodate the stage-specific expression of various proteins essential to the parasite development. It is possible that PfArf is the major regulator of ER to Golgi transport in the asexual stages of parasites, while PfRab1 has a similar function in the sexual stages of parasites. We have identified a chaperone gene encoding the 60 Kda heat shock protein from a P falciparum library. The protein of 577 amino acids contains a putative mitochondrial targeting peptide at its amino-terminus and a -GGM motif at its carboxyl-terminus. During heat shock the level of hsp60 transcript in blood stage parasites increases signifiantly and its accumulation correlates with the duration of the induction. We have also expressed Pfhsp60 in E Coli and used to raise specific antibody in rabbits. Pfhsp60 is under investigation for its role in parasite growth and in the host immune response (stimulation of gamma/delta T cells) to malaria infection.